Cleft palate is among the most common craniofacial malformations, affecting one in every 1000 live births worldwide. Cleft palate can be a part of genetic syndromes and also can occur as an isolated or non-syndromic birth defect. Non-syndromic cleft palate is a complex trait and can be due to genetic abnormalities, environmental influences or the combination of both that disturb secondary palate development. The mammalian secondary palate is formed by fusion of two separate palatal shelves that are derived from the maxillary processes. After initial vertical growth on either side of the tongue, the palatal shelves undergo an elevation process and move into a horizontal position above the tongue where the opposing shelves approximate each other for contact and fusion. Failure or delay of palatal shelf elevation is a common cause of cleft palate. In this application, we will develop new experimental approaches to validate different models of palatal shelf elevation and to further elucidate the mechanism of palatal shelf elevation. We propose two specific aims for this research project: 1) to determine if palatal shelf elevation results from shelf mechanical rotation or from shelf shape changes or remodeling; 2) to determine the role of hyaluronic acid in palatal morphogenesis. To achieve these aims, we will combine ex vivo shelf elevation with dye labeling of palatal cells to examine shelf elevation behaviors and use the mouse genetic approach to study the function of mesenchymal hyaluronic acid during palatal shelf elevation. The results of these studies will refine and improve our knowledge on palate development and pathogenesis of cleft palate, which is important for developing methods that could promote palatal shelf elevation and reduce chances of cleft palate formation.